Hypercholesterolemia in ExHC rats and lipid-lowering drug: a screening method for new hypocholesterolemic agents.
The ExHC rat strain which was selected and bred from the Sprague-Dawley strain, develops severe hypercholesterolemia and is liable to aortic lipid deposition when the rats are fed an atherogenic diet. After only 4 days on the atherogenic diet, hypercholesterolemia was induced in these ExHC rats. Following a study of gel-filtration and SDS-disc electrophoresis, significant increases of broad-LDL (beta-VLDL) and of apo E and apo B were noted. On the other hand, plasma HDL and its major apolipoprotein, apo A-I, showed decreases. All these changes might be responsible for the future induction of aortic lipid deposition. A screening method for new hypocholesterolemic agents which takes advantage of these ExHC rat characteristics has been set up; it involves the evaluation of cholesterol lowering and HDL increasing effects by the determination of plasma cholesterol and by radioimmunoassay of apo A-I, respectively. Although clofibrate (100 mg/kg body weight) reduced plasma cholesterol levels significantly, there was no apo A-I increasing effect.
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D016632:Apolipoprotein A-I; D001053:Apolipoproteins / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D009115:Muridae; D051381:Rats
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D002994:Clofibrate